Petukhov et al. [Petukhov P A, Zhang J, Kozikowski A P, Wang C Z, Ye Y P, Johnson K M and Tella S R]; J. Med. Chem. 2002 45 3161-3170] describe SAR studies of piperidine-based analogues of cocaine.
WO 00/20390 (Georgetown University) describes monomeric and dimeric heterocycles and therapeutic uses thereof.
WO 98/51668 (NeuroSearch A/S) describes 3-alkoxyimidomethyl-piperidine derivatives active as neurotransmitter re-uptake inhibitors. Examples 1 and 2 describe two intermediate mixtures, (±)-cis/trans-1-methyl-3-methoxycarbonyl-4-(3,4-dichlorophenyl)-piperidine and (±)-cis/trans-1-methyl-3-hydroxymethyl-4-(3,4-dichlorophenyl)-piperidine. No pharmacological use of these two intermediate mixtures is disclosed.
However, there is a continued strong need to find compounds with an optimised biochemical profile as regards the activity on reuptake of the monoamine neurotransmitters serotonin, dopamine and noradrenaline, such as the ratio of the serotonin reuptake versus the noradrenaline and dopamine activity.
Furthermore, there is a strong need to find effective compounds, which structurally and synthetically wise are unrelated to cocaine.